LIMIT Trial: Lidocaine with Intramuscular Injection of Benzathine Penicillin G for Treponema pallidum Treatment

Why clinicians should know about it

• Picked for Dermatology (top studies of the week, 1 November 2026): RCT showing lidocaine reduces penicillin injection pain

Abstract

BACKGROUND: Studies have shown that intramuscular benzathine penicillin G (BPG) or bicillin injections cause severe pain in many patients, which may reduce adherence. Local anesthetics mixed with BPG may reduce injection pain without affecting drug effectiveness. The objective of this study was to examine if there is any benefit of adding 0.5 ml 1% lidocaine to prepackaged Benzathine Penicillin G, with respect to pain, compared to standard of care, in the treatment of Treponema pallidum infections, both 10 minutes and 24 hours after injection. METHODS: This study is a double blinded randomized placebo control trial of the effect on pain of the addition of 0.5ml 1% lidocaine solution to prepackaged BPG injection, compared to addition of 0.5 ml normal saline solution, in adults being treated for syphilis (Treponema pallidum) infections, within the Infectious Diseases Clinic at Washington University in St. Louis. RESULTS: Preliminary analysis included 15 participants. A Wilcoxon Signed-Rank Test indicated a statistically significant reduction in pain 10 minutes after lidocaine injection compared to the saline injection (z = -2.65, p = 0.008). The mean pain score following administration after 10 minutes of the lidocaine solution was 3, compared to 6.73 for the saline solution. Overall, 87% of participants reported at least a 2-point reduction in pain scores after 10 minutes with lidocaine relative to saline. However, no significant difference in pain scores was observed between the two solutions at the 24-hour follow-up. CONCLUSION: This trial demonstrates that lidocaine can help reduce the pain associated with intramuscular injections of BPG.

Abstract as published, via PubMed.